Asinger reaction explained

The Asinger-reaction (sometimes referred to as the Asinger-4 component reaction or A-4CR for short) is a multicomponent reaction for the synthesis of 3-thiazolines and other related heterocycles.^[1] It is named after Friedrich Asinger who first reported it in 1956.^[2]

Process

An α-halogenated carbonyl-component reacts with sodium hydrosulfide (NaSH) and forms a Thiol in situ. The thiol reacts directly with another carbonyl component and ammonia to form a thiazoline. The reaction works also by using elemental sulphur, an α–substituted ketone, another carbonyl component and ammonia; in this case, a mixture of products is formed.

The formation of 3-thiazolines also occurs by using α-thioaldehyde or α-thioketone and ammonia.^[3]

A simplified route of the Asinger-reaction was developed at Degussa. An α-halogenated carbonyl compound reacts with sodium hydrosulfide (NaSH) and forms a thiol in situ which reacts directly with aldehydes or ketones and ammonia to 3-thiazolines.^[4] The chemical industry developed based on the Asinger-reaction multi stage processes for the production of pharmaceuticals like D-penicillamine^[5] and the aminoacid DL-cysteine.^[6]

Literature

• Angewandte Chemie . 68 . 11 . 1956. 377. 10.1002/ange.19560681109. Chemiker-Treffen Salzburg: Über die einfache und ergiebige Synthese von Thiazolonen . Friedrich Asinger.
• Angewandte Chemie . 68 . 12 . 1956 . 413 . 10.1002/ange.19560681209 . Über die gemeinsame Einwirkung von Schwefel und Ammoniak auf Ketone . Friedrich Asinger. 1956AngCh..68..413A.
• Tetrahedron Letters . 41 . 38 . 2000 . 7289 - 7292 . 10.1016/S0040-4039(00)01266-1 . Synthesis of the first enantiomerically pure 3-thiazolines via Asinger reaction . Imre Schlemminger . Hans-Hermann Janknecht . Wolfgang Maison . Wolfgang Saak . Jürgen Martens.

Notes and References

1. Asinger . F. . Offermanns . H. . Syntheses with ketones, sulfur, and ammonia or amines at room temperature . Angewandte Chemie International Edition in English . November 1967 . 6 . 11 . 907–919 . 10.1002/anie.196709071.
2. Asinger . F. . Über die gemeinsame Einwirkung von Schwefel und Ammoniak auf Ketone . Angewandte Chemie . 21 June 1956 . 68 . 12 . 413 . 10.1002/ange.19560681209. 1956AngCh..68..413A.
3. Asinger . F. . Thiel . M. . Einfache Synthesen und chemisches Verhalten neuer heterocyclischer Ringsysteme . Angewandte Chemie . 26 November 1958 . 70 . 22–23 . 667–683 . 10.1002/ange.19580702202. 1958AngCh..70..667A.
4. Drauz . Karlheinz . Koban . Hans Günter . Martens . Jürgen . Schwarze . Wolfgang . Phosphonic and Phosphinic Acid Analogs of Penicillamine . Liebigs Annalen der Chemie . 12 March 1985 . 1985 . 3 . 448–452 . 10.1002/jlac.198519850303.
5. Weigert . Wolfgang M. . Offermanns . Heribert . Scherberich . Paul . D-Penicillamin - Herstellung und Eigenschaften . Angewandte Chemie . May 1975 . 87 . 10 . 372–378 . 10.1002/ange.19750871003. 1975AngCh..87..372W.
6. Martens . Jürgen . Offermanns . Heribert . Scherberich . Paul . Einfache Synthese von racemischem Cystein . Angewandte Chemie . August 1981 . 93 . 8 . 680–683 . 10.1002/ange.19810930808. 1981AngCh..93..680M.